MRP1 protein expression in leukemic stem cells as a negative prognostic marker in acute myeloid leukemia patients

• Published in: European journal of haematology Vol. 99; no. 5; pp. 415 - 422
• Main Authors: Paprocka, Maria, Bielawska‐Pohl, Aleksandra, Rossowska, Joanna, Krawczenko, Agnieszka, Duś, Danuta, Kiełbiński, Marek, Haus, Olga, Podolak‐Dawidziak, Maria, Kuliczkowski, Kazimierz
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.11.2017
• Subjects: Acute myeloid leukemia; Adult; Aged; Aged, 80 and over; Antibodies; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; BCRP; Biomarkers, Tumor; Bone marrow; Bone Marrow Cells - metabolism; Bone Marrow Cells - pathology; CD123 antigen; CD34 antigen; CD38 antigen; Chemotherapy; Drug resistance; Female; Flow Cytometry; Gene Expression; Humans; Immunophenotyping; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - mortality; leukemic stem cells; Male; MDR1; MDR1 protein; MDR3; Middle Aged; MRP1 and LRP; MRP1 protein; Multidrug resistance; multidrug resistance proteins; Multidrug Resistance-Associated Proteins - genetics; Multidrug Resistance-Associated Proteins - metabolism; Myeloid leukemia; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; P-Glycoprotein; Prognosis; prognostic markers; Protein expression; Proteins; Remission; Stem cells; Treatment Outcome; BCRP; MDR1; MRP1 and LRP; prognostic markers; leukemic stem cells; multidrug resistance proteins; MDR3
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.12938

Background It is well established that expression of multi‐drug resistance (MDR) proteins (MDR1, BCRP, MDR3, MRP1, and LRP) in leukemic blasts correlates with acute myeloid leukemia (AML) patients’ clinical response. Assuming that leukemic stem cells (LSC) are resistant to chemotherapy and responsible for relapse, it might be clinically relevant to evaluate the expression level of MDR proteins in LSC and relate it to the clinical outcome. Methods Bone marrow samples from 26 patients with de novo AML were labeled with antibodies to distinguish CD34+CD38−CD123+ LSC population and with antibodies against MDR1, BCRP, MDR3, MRP1, or LRP proteins. Multicolor flow cytometry was applied to evaluate the expression of MDR proteins in blasts and LSC. Results Nine of 26 patients with AML attained CR (30%). High negative correlation was found between MDR1 and LRP expression in blasts and the patient's remission. MDR proteins were expressed more frequently in LSC than in leukemic blasts. High negative correlation was also observed between remission achievement and MRP1 expression in LSC. Conclusions Our data present for the very first time the high negative correlation between MRP1 protein expression in LSC and AML patients’ remission. It does strongly suggest that MRP1 expression in LSC is an adverse prognostic marker in patients with de novo AML.